A team of researchers at New York University has found that the nucleus of a human cell exhibits subtle, but measurable, fast shape fluctuations, and that the amplitude of these fluctuations systematically decreases during the cell cycle, thus serving as a cell cycle stage indicator. The findings, published in the Proceedings of the National Academy of Sciences, create new opportunities for understanding the building blocks of life and the onset of disease.
Human cell nuclei with fluorescently labeled chromatin (purple) and nuclear envelope (green). Image credit: Fang-Yi Chu & Alexandra Zidovska, New York University.
“Previously, a precise point of a cell in its life cycle could only be determined by studying dead cells. However, with this discovery, which shows that the nucleus exhibits rapid fluctuations that decrease during the life cycle of the cell, we can enhance our knowledge of both healthy and diseased human cells,” said study senior author Dr. Alexandra Zidovska, an assistant professor of physics at New York University.
The study sought to expand our understanding of the cell nucleus during the cell cycle.
“It’s long been established that the shape and size of the cell nucleus change dramatically during a cell’s life,” the researchers said.
“Unknown, however, was whether or not the nucleus changes its shape over short periods of time. This was largely due to technical limitations of carrying out such measurements in living cells.”
To capture this dynamic, Dr. Zidovska and her colleagues, Fang-Yi Chu and Shannon Haley, used a state-of-the-art fluorescent microscope that enables them to see extremely small and very fast shape changes of the cell nucleus in living cells.
They discovered that the human cell nucleus has a previously undetected type of motion: its nuclear envelope flickers (fluctuates) over a period of a few seconds.
Notably, the amplitude of these changes in shape decreases over time during the cell cycle.
Moreover, this motion marks the first physical feature that systematically changes with the cell cycle.
“Our findings reveal that nuclear envelope flickers, i.e., undulates at time scales of seconds, with active undulations driven by both chromatin and cytoskeleton. The amplitude of these undulations provides us with an internal cell cycle stage indicator,” the scientists said.
“The possible role of such undulations is yet to be revealed.”
“This process can serve as an internal clock of the cell, telling you at what stage in the cell cycle the cell is,” Dr. Zidovska added.
“We know that structural and functional errors of the nuclear envelope lead to a large number of developmental and inherited disorders, such as cardiomyopathy, muscular dystrophy, and cancer.”
“Illuminating the mechanics of nuclear shape fluctuations might contribute to efforts to understand the nuclear envelope in health and disease.”
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Fang-Yi Chu et al. On the origin of shape fluctuations of the cell nucleus. PNAS, published online September 12, 2017; doi: 10.1073/pnas.1702226114
